Diseases of the Neuromuscular Junction and Motor Unit Flashcards
1
Q
describe lesions of the soma
A
- diseases
- ALS
- poliomyelitis
- manifestations
- muscle atrophy and weakness
- hyporeflexia
- fasciculations and fibrillations
- eventual loss of muscle fibers (replaced by non-contractile fibrous CT)
2
Q
describe poliomyelitis
A
- viral infection primarily attacking ventral spinal grey matter
- etiology:
- small RNA viruses of Enterovirus genus
- transmission is via fecal-oral route and aerosol droplets
- clinical features
- profound asymmetrical muscle weakness
- affected limbs become floppy and poorly controlled - acute flaccid paralysis (AFP)
3
Q
describe clinical features of poliomyelitis
A
- destroyed motor neurons do not regenerate and denervated uscles will be unable to contract
- extesive paralysis of the trunk may occur
- mid-cervical involvement (C3,4,5) can paralyze diaphragm, necessitating ventilation
- the tank respirator (iron lung) has some advantages over positive pressure applied through a tracheostomy and is still used occasionally
4
Q
describe diseases related to lesions of Schwann cells
A
- Guillain-Barre
- diphtheria
5
Q
describe the effect of botulinum toxin
A
- botulinum toxin
- toxic anerobic bacterial protease that reduces ACh release by acting on presynaptic exocytotic proteins
6
Q
describe the mechanism of action of alpha-latrotoxin
A
- toxin in venom of the black widow spider that causes massive release of ACh
7
Q
describe the mechanism of action of beta-bungarotoxin
A
- toxin in venom of snake initially provokes ACh release followed by ACh depletion by acting on proteins in nerve terminals involved in exocytosis
8
Q
describe the mechanism of action of curare (delta-tubocurarine)
A
- blocks nAChRs
9
Q
describe Lambert-Eaton syndrome
A
- this is a presynaptic disorder of neuromuscular transmission in which release of ACh is affected
- strength increases with sustained or repeated muscular contraction in otherwise weakened patients because of the increase in concentration of synaptic ACh
- etiology:
- autoimmune disease where antibodies attack presynaptic voltage-gated Ca channels
10
Q
describe the physiological changes at the end plate in Lambert-Eaton syndrome
A
- amplitude of miniEPP is unchanged
- reduced amplitude of EPP
- reduced quantal content
- many EPPs do not attain threshold in muscle fibers
- waxing response in EMG (relates to facilitating neuromuscular block)
11
Q
describe the EMG
A
12
Q
describe the treatment of Lambert-Eaton syndrome
A
- removal of underyling tumor and immunosuppressive drugs
- plasma exchange
- calcium gluconate to enhance Ca influx into nerve terminal
- 4-aminopyridine (potassium channel blocker) to prolong presynaptic action potential and improve transmitter release
13
Q
describe the deficiency of ACh-esterase can lead to myasthenia
A
- deficiency of ACh-esterase in synaptic cleft
- EPP amplitude is larger and longer than normal
- single motor nerve stimuli delivered at low freq. cause single muscle twitches
- high-freq. motor nerve stimuli produce temporal summations of EPPs and cause depolarization block of muscle
14
Q
describe how slow channel syndrome can lead to myasthenia
A
- ACh binding to nAChRs causes prolonged opening of ACh receptor channels and consequently, depolarization block
- inherited rare-condition presents at birth or early childhood
- muscle weakness
- rapid fatigue
15
Q
describe myasthenia gravis
A
- chronic autoimmune diseases with antibodies to nAChRs develop and reduce transmission at the NMJ
- symptoms:
- weakness of somatic muscles
- not associated with denervation
- fatigability
- temporary restoration of strength after rest
- weakness of somatic muscles
16
Q
describe the interaction of antibody and nAChR
A
- antibodies bind to alpha subunits of nAChR
- antibodies do not compete with ACh for binding sites on subunits
- antibodies cross-link neighboring nAChRs
- endocytosis of nAChRs in endplate membranes –> lysosomal destruction
- enhanced removal rate of nAChRs but no enhanced rate of insertion of nAChRs into end plate membrane
- fall of density of nAChRs at end plate
17
Q
A
18
Q
describe the diagnosis and treatment of MG
A
- diagnosis
- repeated clenching/unclenching of fist -> weakness
- Tensilon test (edrophonium), which is a ACh-esterase inhibitor, so muscular strength recovers temporarily
- treatment
- immunosuppressing medication: azathioprine, corticosteroids
- pyridostigmine (AChE inhibitor)
19
Q
describe lesion of the chloride channel (myotonia congenita)
A
- autosomal dominant disease, influencing the gene encoding Cl channels in the muscle membrane
- leads to a small number of chloride channels in muscle
- in normal muscles, the numerous Cl channels help to keep the membrane potential close to ECl during recovery from an action potential
- there is increased excitability; smaller depolarization is required to evoke an AP and may even cause a train of APs
- K accumulation in trasverse tubular system causes some depol. leading to spontaneous firing of the muscle after the end of nerve stimulation
20
Q
describe Duchenne muscular dystrophy
A
- X-linked recessive disorder os muscles in males
- cause: absence of muscle protein, dystrophin
21
Q
describe LMN syndrome
A
- lower motor neurons
- primary motor neurons of the spinal cord and brain stem that directly innervate skeletal muscles
- signs:
- muscle weakness (paresis)
- flaccid paralysis
- hyporeflexia
- fasciculations
- fibrilliations
- upper motor neurons
- neurons that originate in higher regions of the brain (cortex) and synapse on LMNs
22
Q
describe the expression of nAChRs in normal muscles
A
- nAChRs scatter broadly but sparsely across embryonic muscle cells
- in adult muscle fibers, normal nerve stimulation leads to aggregation of nAChRs under nerve endings
23
Q
explain the expression of nAChRs in denervated muscles
A
- following denervation, nAChRs return to a supersensitive embryonic state with an adult state re-emerging with reinnervation
